Endocrine and Metabolic Flashcards

Question

What is the presentation of diabetes insipidus?

Answer 1

--> Polyuria (producing more than 3 litres of urine per day) --> Polydipsia (excessive thirst) --> Dehydration --> Postural hypotension

Answer 2

--> The water deprivation test is the test of choice for diagnosing diabetes insipidus. --> Low urine osmolality (lots of water diluting the urine) --> High/normal serum osmolality (water loss may be balanced by increased intake) --> More than 3 liters on a 24-hour urine collection

Answer 3

Procedure: --> No fluids for up to 8 hours. --> Measure urine osmolality after deprivation. --> If low, administer desmopressin and measure urine osmolality over 2-4 hours. Interpretation: Primary Polydipsia: --> High urine osmolality after water deprivation. --> Desmopressin not needed. --> Diagnosis: Rules out diabetes insipidus. Cranial Diabetes Insipidus: --> Low urine osmolality after water deprivation. --> High urine osmolality after desmopressin. Nephrogenic Diabetes Insipidus: --> Low urine osmolality both before and after desmopressin.

Answer 4

The underlying cause should be treated (e.g., stopping lithium). Mild cases may be managed conservatively. Desmopressin (synthetic ADH) can be used in cranial diabetes insipidus to replace the absent antidiuretic hormone. The serum sodium needs to be monitored, as there is a risk of hyponatraemia (low sodium) with desmopressin. Nephrogenic diabetes insipidus is less straightforward to treat. Management options include: Ensuring access to plenty of water High-dose desmopressin Thiazide diuretics NSAIDs

Answer 5

Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans of the pancreas. This process is thought to be influenced by a combination of genetic and environmental factors.

Answer 6

--> Mechanism: Type IV hypersensitivity autoimmune reaction where CD4+ T helper and CD8+ cytotoxic T cells attack pancreatic beta cells. --> Progression: Beta cell destruction occurs over months to years, leading to hyperglycemia when ~90% of beta cells are destroyed. --> Alpha Cell Dysfunction: Beta cell loss also affects alpha cells, causing excessive glucagon release, which leads to gluconeogenesis, glycogenolysis, and ketogenesis, worsening hyperglycemia and causing diabetic ketoacidosis.

Answer 7

Typical Onset: Predominantly in childhood, most commonly diagnosed between ages 10-14. Triad of Symptoms: Polydipsia: Increased thirst due to hyperglycemia and fluid loss from polyuria. Polyuria/Nocturia: Excessive urination due to renal glucose excretion and increased fluid intake. Weight Loss: Loss of calories through glucose in urine. Additional Symptoms: Dry Mouth: Caused by dehydration from polyuria. Lethargy: Due to lack of glucose uptake by cells. Blurred Vision: Acute swelling of the lens from hyperglycemia. Young Children: Symptoms may be hard to identify; look for Candida infections in the groin as a possible indicator.

Answer 8

--> Fasting blood glucose ≥7.0 mmol/L (≥126 mg/dL) --> Non-fasting blood glucose ≥11.1 mmol/L (≥200 mg/dL) --> Oral glucose tolerance test (OGTT): Blood glucose ≥11.1 mmol/L, 2 hours after 75 g glucose --> HbA1c ≥48 mmol/mol (≥6.5%)

Answer 9

--> Autoantibodies (islet cells, IA2, GAD, ZnT8) indicate autoimmune beta cell destruction. --> Fasting C-peptide is low or undetectable, indicating low endogenous insulin production.

Answer 10

--> Age: Usually in childhood/adolescence --> Clinical presentation: Polyuria, polydipsia, weight loss, lethargy, DKA Ketosis: Often present, may lead to DKA --> Autoantibodies: Islet cells, insulin, IA2, GAD, ZnT8 --> C-peptide: Low or undetectable (reflects low endogenous insulin production)

Answer 11

--> T2DM results from insulin resistance with relative insulin deficiency. --> Slower onset and older age at diagnosis. Ketosis uncommon. --> Strong association with obesity and family history of T2DM. --> Negative autoantibodies. --> May respond to oral anti-hyperglycaemic drugs.

Answer 12

Prolonged use of corticosteroids, tacrolimus, L-asparaginase, or antipsychotics.

Answer 13

Cystic fibrosis, chronic pancreatitis, hereditary haemochromatosis.

Answer 14

Genetic factors: Over 100 susceptibility loci identified by GWAS, involved in insulin secretion, action, and glucose metabolism. Environmental factors: Obesity, physical inactivity, and high-calorie diets increase risk; diets rich in fiber, whole grains, and unsaturated fats reduce it. Age & ethnicity: Risk increases after age 45, and certain ethnic groups (African Americans, Hispanics, Asians, Native Americans) are at higher risk.

Answer 15

--> insulin resistance: Caused by increased free fatty acids, pro-inflammatory cytokines, ectopic fat deposition, and oxidative stress, leading to impaired glucose uptake and increased hepatic glucose production. --> β-cell dysfunction: Results from glucotoxicity, lipotoxicity, chronic inflammation, and amyloid deposition, causing reduced insulin secretion and eventual β-cell failure.

Answer 16

--> Asymptomatic (70%): Diagnosed on routine screening with hyperglycemia (fasting glucose >6.9 mmol/L, HbA1c >48 mmol/mol). --> Subacute: Polyuria, fatigue, blurred vision, polydipsia, weight loss, nocturia, pruritis vulvae/balanitis (Candida infections). --> Acute: Rare presentation with hyperosmolar hyperglycemic state (HHS), severe dehydration, and marked hyperglycemia without ketoacidosis. --> Complications: 25% present with microvascular complications (e.g., retinopathy, nephropathy) at diagnosis.

Answer 17

Symptomatic: Fasting glucose ≥7.0 mmol/L Random glucose ≥11.1 mmol/L (or 2h post-75g glucose load) Asymptomatic: Same criteria but must be confirmed on two occasions. HbA1c: ≥48 mmol/mol (6.5%) is diagnostic, but repeat test required for asymptomatic patients. Conditions where HbA1c is unreliable: Haemoglobinopathies, haemolytic anemia, untreated iron deficiency anemia, suspected gestational diabetes, children, HIV, chronic kidney disease, steroid use.

Answer 18

--> Impaired Fasting Glucose (IFG): Fasting glucose ≥6.1 but <7.0 mmol/L. --> Impaired Glucose Tolerance (IGT): Fasting glucose <7.0 mmol/L and 2-hour OGTT value ≥7.8 but <11.1 mmol/L. --> Diabetes UK Guidance: For IFG, an OGTT should be performed. If the OGTT result is between 7.8 and 11.1 mmol/L, it confirms IGT, not diabetes.

Answer 19

--> Lifestyle alone or lifestyle + metformin: HbA1c target is 48 mmol/mol (6.5%). --> Lifestyle + drugs causing hypoglycemia (e.g., sulfonylureas): HbA1c target is 53 mmol/mol (7.0%). --> If already on one drug and HbA1c rises to 58 mmol/mol (7.5%): Adjust target to 53 mmol/mol (7.0%).

Answer 20

--> Metformin: First-line drug; titrate slowly to minimize gastrointestinal issues. Use modified-release if standard-release is not tolerated. --> If metformin is contraindicated: Use SGLT-2 inhibitors (if CVD risk, established CVD, or chronic heart failure), otherwise DPP-4 inhibitors, pioglitazone, or sulfonylureas.

Answer 21

--> Second-line: Add one of the following to metformin: DPP-4 inhibitor, pioglitazone, sulfonylurea, or SGLT-2 inhibitor (if NICE criteria met). --> Third-line: Add another drug or insulin if needed: metformin + DPP-4 inhibitor + sulfonylurea, or pioglitazone + sulfonylurea, or insulin.

Answer 22

Start insulin: Continue metformin; begin with human NPH insulin (intermediate-acting). GLP-1 mimetics: Consider if BMI ≥35 kg/m² with obesity-related issues or if insulin therapy has significant implications. Continue only if HbA1c drops by at least 11 mmol/mol (1.0%) and weight loss is ≥3% in 6 months.

Answer 23

--> Hypertension: Aim for clinic BP targets of 140/90 mmHg (age <80) or 150/90 mmHg (age >80). Use ACE inhibitors or ARBs; ARB preferred for black African or African-Caribbean origin. --> Lipids: Statins recommended if 10-year cardiovascular risk >10%. First-line: atorvastatin 20 mg.

Answer 24

Increases insulin sensitivity and decreases liver glucose production.

Answer 25

Gastrointestinal issues (pain, nausea, diarrhea), and rare lactic acidosis (especially with acute kidney injury).

Answer 26

They can try modified-release Metformin.

Answer 27

Blocks glucose reabsorption in the kidneys, increasing glucose excretion in urine.

Answer 28

Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin.

Answer 29

Glycosuria, increased urination, genital and urinary tract infections, weight loss, and rare Fournier’s gangrene and lower-limb amputation (more common with Canagliflozin).

Answer 30

Increases insulin sensitivity and decreases liver glucose production.

Answer 31

Weight gain, heart failure, increased risk of bone fractures, and a small increase in bladder cancer risk.

Answer 32

Gliclazide

Answer 33

Stimulate insulin release from the pancreas.

Answer 34

Weight gain and hypoglycemia.

Answer 35

--> Insulin Deficiency: Causes hyperglycemia, ketosis, and metabolic acidosis. --> Hyperglycemia: Due to increased gluconeogenesis and glycogenolysis in the liver, and decreased glucose utilization in peripheral tissues. --> Ketosis: Insulin deficiency leads to lipolysis, producing free fatty acids converted to ketone bodies (β-hydroxybutyrate and acetoacetate) in the liver. --> Metabolic Acidosis: Accumulation of ketone bodies causes an anion gap metabolic acidosis. --> Common Triggers: Infection, missed insulin doses, and myocardial infarction.

Answer 36

DPP-4 inhibitors block the DPP-4 enzyme, increasing incretin activity. Examples include sitagliptin and alogliptin.

Answer 37

Rapid-acting insulin (e.g., NovoRapid) starts working in about 10 minutes and lasts for approximately 4 hours.

Answer 38

GLP-1 mimetics imitate the action of GLP-1, increasing insulin secretion and slowing glucose absorption. Examples include exenatide and liraglutide.

Answer 39

--> Triad: Hyperglycemia, ketosis, metabolic acidosis. --> Hyperglycemia: Blood glucose >11 mmol/L, causing polyuria, polydipsia, blurred vision, headache, lethargy. --> Acidosis: pH <7.3, bicarbonate <15 mmol/L; Kussmaul breathing (deep, rapid) to expel CO₂. --> Ketosis: Sweet, fruity or acetone breath odor; due to increased ketone bodies. --> Dehydration: Dry mucous membranes, tachycardia, hypotension, decreased skin turgor; electrolyte imbalances (e.g., hypokalemia). --> Neurological Symptoms: Altered mental status, possible seizures. --> Abdominal Symptoms: Pain, nausea, vomiting, can mimic acute abdomen. --> Precipitating Factors: Infections, poor insulin compliance, newly diagnosed diabetes, myocardial infarction.

Answer 40

Glucose: >11 mmol/L or known diabetes mellitus pH: <7.3 Bicarbonate: <15 mmol/L Ketones: >3 mmol/L or urine ketones ++ on dipstick

Answer 41

--> Fluid Replacement: Most patients are depleted by 5-8 liters. Start with isotonic saline, even if acidotic. Insulin: Begin intravenous infusion at 0.1 unit/kg/hour. When glucose <14 mmol/L, add 10% dextrose at 125 mL/hr. --> Electrolyte Correction: Serum potassium often high initially but total body potassium is low. Monitor and potentially add potassium to replacement fluids. Cardiac monitoring required if potassium infusion >20 mmol/hour. --> Insulin Management: Continue long-acting insulin. Discontinue short-acting insulin.

Answer 42

--> Gastric Stasis: Impaired gastric motility. --> Thromboembolism: Increased risk of VTE due to dehydration and hypercoagulability; consider VTE prophylaxis. --> Arrhythmias: Can be caused by hyperkalaemia or iatrogenic hypokalaemia. --> Cerebral Oedema: Rare, particularly in children; manifests as headache, altered mental status, seizures. Usually occurs 4-12 hours after treatment starts. Seek CT head and senior review if suspected. --> Acute Respiratory Distress Syndrome --> Acute Kidney Injury --> Hypoglycaemia and Hypokalaemia: Can occur due to incorrect fluid therapy.

Answer 43

--> Hyperglycaemia leads to osmotic diuresis, causing loss of sodium and potassium. --> Severe Volume Depletion results in high serum osmolarity (>320 mosmol/kg) and hyperviscosity of blood. --> Dehydration may be less apparent due to hypertonicity preserving intravascular volume.

Answer 44

--> General: Fatigue, lethargy, nausea, vomiting --> Neurological: Altered level of consciousness, headaches, papilloedema, weakness --> Haematological: Hyperviscosity (can cause myocardial infarctions, stroke, peripheral arterial thrombosis) --> Cardiovascular: Dehydration, hypotension, tachycardia

Answer 45

--> Hypovolaemia --> Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis --> Significantly Raised Serum Osmolarity (>320 mosmol/kg)

Answer 46

--> Normalise Osmolality (Gradually): Fluid losses in HHS are 100-220 ml/kg. Use IV 0.9% sodium chloride initially. Switch to 0.45% sodium chloride if osmolality doesn’t decline. Aim to replace 50% of fluid loss in the first 12 hours and the remainder in the next 12 hours. Avoid rapid changes in serum osmolarity; monitor hourly. A safe reduction rate for blood glucose is 4-6 mmol/hr. Aim for a target of 10-15 mmol/L. Complete normalization may take up to 72 hours. --> Fluid Replacement: Start with IV 0.9% sodium chloride, adjusting to 0.45% if needed. Avoid rapid rehydration, especially in those with heart failure or chronic kidney disease. --> Insulin: Only start if significant ketonaemia is present (β-hydroxybutyrate >1 mmol/L). Use IV insulin infusion at 0.05 units/kg/hr. Avoid insulin if ketonaemia is not significant, as it can cause rapid osmolarity changes. --> Electrolyte Correction: Monitor and replace potassium as necessary. Potassium levels can be affected by insulin and fluid replacement. Cardiac monitoring is needed if potassium infusion exceeds 20 mmol/hr. --> Monitoring Response: Track serum osmolarity, sodium, and glucose levels. A rise in serum sodium with decreasing glucose is expected but should be monitored. Avoid a sodium rise greater than 2.4 mmol/L for each 5.5 mmol/L fall in glucose.

Answer 47

Short-acting insulin (e.g., Actrapid) starts working in around 30 minutes and lasts about 8 hours.

Answer 48

Intermediate-acting insulin (e.g., Humulin I) starts working in about 1 hour and lasts for around 16 hours.

Answer 49

Long-acting insulin (e.g., Levemir, Lantus) starts working in about 1 hour and lasts 24 hours or longer.

Answer 50

Humalog 25: 25% rapid-acting, 75% intermediate-acting Humalog 50: 50% rapid-acting, 50% intermediate-acting Novomix 30: 30% rapid-acting, 70% intermediate-acting

Answer 51

early morning

Answer 52

An ACR greater than 2.5.

Answer 53

Dietary protein restriction.

Answer 54

Less than 130/80 mmHg.

Answer 55

If urinary ACR is 3 mg/mmol or more.

Answer 56

Sensory loss with a 'glove and stocking' distribution.

Answer 57

Amitriptyline, duloxetine, gabapentin, or pregabalin.

Answer 58

Erratic blood glucose control, bloating, and vomiting.

Answer 59

Metoclopramide, domperidone, or erythromycin.

Answer 60

Decreased lower esophageal sphincter (LES) pressure.

Answer 61

Potassium and hydrogen ions compete; higher potassium levels reduce hydrogen ion entry into cells.

Answer 62

Vomiting Thiazide and loop diuretics Cushing's syndrome Conn's syndrome (primary hyperaldosteronism).

Answer 63

RAPID mnemonic Renal tubular acidosis Acetazolamide Partially treated diabetic ketoacidosis. Diarrhoea

Answer 64

It can cause hypokalaemia, and normalizing potassium levels may be difficult until magnesium deficiency is corrected.

Answer 65

In Hypokalaemia, U have no Pot and no T, but a long PR and a long QT U waves No T waves or small Long PR Long QT ST depression

Answer 66

--> muscle weakness, hypotonia --> hypokalaemia predisposes patients to digoxin toxicity - care should be taken if patients are also on diuretics

Answer 67

Hydrogen and potassium ions compete for exchange with sodium ions across cell membranes and in the distal tubule.

Answer 68

Tall-tented T waves, small P waves, widened QRS leading to a sinusoidal pattern, and asystole.

Answer 69

RAAMMD mnemonic Rhabdomyolysis Acute kidney injury Addison's disease Metabolic acidosis Massive blood transfusion. Drugs (potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor blockers, spironolactone, ciclosporin, heparin)

Answer 70

Potassium chloride (oral)

Answer 71

Beta-blockers interfere with potassium transport into cells, potentially causing hyperkalaemia in renal failure. Both unfractionated and low-molecular weight heparin can cause hyperkalaemia by inhibiting aldosterone secretion.

Answer 72

Mild: 5.5 - 5.9 mmol/L Moderate: 6.0 - 6.4 mmol/L Severe: ≥ 6.5 mmol/L

Answer 73

Peaked or 'tall-tented' T waves Loss of P waves Broad QRS complexes Sinusoidal wave pattern

Answer 74

Stabilisation of cardiac membrane: IV calcium gluconate (does NOT lower serum potassium). Short-term shift of potassium: Insulin/dextrose infusion, nebulised salbutamol. Removal of potassium: Calcium resonium (oral/enema), loop diuretics, dialysis, haemofiltration/haemodialysis for persistent hyperkalaemia with AKI.

Answer 75

Treat the underlying cause if K+ is <6.5 and no ECG changes IF ECG changes and >6.5 then treat with: IV calcium gluconate IV insulin and dextrose

Answer 76

IV calcium gluconate: To stabilise the myocardium. Insulin/dextrose infusion: For short-term potassium shift from ECF to ICF. Other treatments: Nebulised salbutamol for temporary reduction in serum potassium.

Answer 77

Stop exacerbating drugs: e.g., ACE inhibitors. Treat underlying cause. Lower total body potassium: Calcium resonium, loop diuretics, dialysis.

Answer 78

--> Primary hyperparathyroidism is a condition of excess parathyroid hormone (PTH) secretion leading to hypercalcemia. -----> The most common cause is a solitary parathyroid adenoma (85%).

Answer 79

Less common causes include hyperplasia (10%), multiple adenomas (4%), and parathyroid carcinoma (1%).

Answer 80

--> Key risk factors include being female (women are 2-3 times more likely to develop it), --> older age (most common between 55-75 years) --> family history, which increases the risk of multi-gland disease and may suggest MEN.

Answer 81

--> PTH is secreted in response to low serum calcium levels and acts on bones, kidneys, and indirectly the bowels to move calcium into the bloodstream, increasing calcium levels to the normal range. Once normal, PTH secretion decreases.

Answer 82

In primary hyperparathyroidism, certain parathyroid cells fail to respond to the negative feedback from normal calcium levels, continuously secreting PTH, leading to hypercalcemia.

Answer 83

--> Most patients are asymptomatic and are often identified incidentally through raised serum calcium levels discovered during unrelated investigations. They may report mild symptoms such as fatigue, weakness, depression, or cognitive impairment if questioned.

Answer 84

The mnemonic 'stones, bones, abdominal groans, and psychic overtones': --> Stones: Increased risk of kidney stones (17%) --> Bones: Bone pain (35%), osteopenia and osteoporosis (40%) --> Abdominal groans: Abdominal pain, constipation, nausea, vomiting --> Psychic overtones: Fatigue, depression (10%), memory impairment (18%)

Answer 85

Other symptoms include polyuria, paresthesia, muscle cramps, and, in severe cases, cardiac/metabolic disturbances, delirium, or coma.

Answer 86

Assess fluid status (due to dehydration risk from polyuria and reduced intake), cognitive function (as hypercalcemia can mimic dementia or depression in the elderly), and screen for signs of malignancy through neck, respiratory, abdominal, breast, and lymphoreticular examinations.

Answer 87

By measuring serum adjusted calcium and parathyroid hormone (PTH) levels simultaneously. Typically, both calcium and PTH are elevated, but a raised calcium with a normal PTH also suggests primary hyperparathyroidism due to inappropriately high PTH levels for the elevated calcium.

Answer 88

Hypercalcemia is defined as serum adjusted calcium >2.6 mmol/L. Primary hyperparathyroidism usually progresses slowly and is mild. If clinical suspicion is high, high-normal calcium levels should be investigated further.

Answer 89

PTH is raised in primary and tertiary hyperparathyroidism. An inappropriately normal PTH in the context of hypercalcemia is also indicative of the disease. Low PTH suggests malignancy or PTH-independent causes of hypercalcemia.

Answer 90

24-hour urinary calcium: High-normal in primary hyperparathyroidism, low in familial hypocalciuric hypercalcemia. eGFR and creatinine: To assess kidney function. Serum/urine protein electrophoresis: To rule out myeloma. Full blood count (FBC): To exclude hematological malignancies. Liver function tests (LFTs): To rule out liver metastases and systemic diseases. DEXA scan: To assess bone health and risk of osteopenia/osteoporosis.

Answer 91

They are usually managed by their GP and then referred to a surgeon for a parathyroidectomy.

Answer 92

Parathyroidectomy is recommended for most patients due to high cure rates (up to 98%) and fewer drug side effects.

Answer 93

Symptomatic hypercalcemia Osteoporosis or fragility fractures Renal stones or nephrocalcinosis Age <50 years Serum adjusted calcium ≥2.85 mmol/L eGFR <60 mL/min/1.73 m²

Answer 94

--> Calcitonin: Inhibits bone and kidney calcium resorption --> Cinacalcet: Calcimimetic that lowers calcium without affecting bone density or urinary calcium --> Denosumab: Inhibits calcium resorption Bisphosphonates

Answer 95

Hypoparathyroidism is an endocrine disorder characterised by deficient or absent parathyroid hormone (PTH) production, resulting in low blood calcium levels and high phosphate levels

Answer 96

Low calcium levels (hypocalcemia) and high phosphate levels (hyperphosphatemia).

Answer 97

--> Post-surgical: Damage or removal of the parathyroid glands during neck surgery, especially thyroidectomy. --> Autoimmune: Destruction of the parathyroid gland, often associated with polyglandular autoimmune syndromes. --> Congenital: Genetic disorders like DiGeorge syndrome causing absent or malfunctioning glands. --> Idiopathic: Unknown cause despite investigation. --> -Metabolic/Nutritional: Prolonged hypomagnesemia or excessive iron/copper deposition (haemochromatosis, Wilson’s disease) damaging the glands. --> Radiation: Damage from radiation therapy to the neck.

Answer 98

--> Reduced PTH Production: Leads to impaired regulation of calcium by acting on bones, kidneys, and intestines. --> Bone Resorption: Less PTH reduces osteoclast activity, lowering calcium release from bones. --> Renal Calcium Reabsorption: Without PTH, more calcium is lost in the urine, worsening hypocalcemia. --> Vitamin D Metabolism: Reduced PTH decreases conversion of vitamin D to its active form (calcitriol), reducing calcium absorption from the intestines. --> Phosphate Handling: PTH normally promotes phosphate excretion. Without it, phosphate retention occurs, reducing free calcium levels.

Answer 99

--> The hallmark is hypocalcemia, presenting with neuromuscular irritability. --> Symptoms range from mild numbness/tingling, muscle cramps, and fatigue to severe manifestations like tetany, carpopedal spasm, laryngospasm, and seizures.

Answer 100

Chvostek's sign: Twitching of the facial muscles in response to tapping over the facial nerve. Trousseau's sign: Carpopedal spasm induced by occluding the brachial artery with a blood pressure cuff.

Answer 101

Extrapyramidal symptoms Cataracts Calcification of the basal ganglia.

Answer 102

Diagnosis is based on low serum calcium, low or inappropriately normal PTH levels, and hyperphosphatemia. Additionally, urinary calcium excretion may be low, and magnesium levels should be checked, especially if magnesium deficiency is suspected.

Answer 103

A prolonged QT interval due to hypocalcemia.

Answer 104

Intracranial calcifications or changes in bone density.

Answer 105

To maintain a slightly low to low-normal serum calcium level to avoid hypercalciuria and renal complications.

Answer 106

Oral calcium supplements Active vitamin D analogues: such as calcitriol or alfacalcidol

Answer 107

Monitoring for symptoms of hypocalcemia and periodic checks of serum calcium, phosphate, magnesium levels, renal function, and urinary calcium excretion.

Answer 108

A high-calcium, low-phosphorus diet.

Answer 109

--> 'bones, stones, groans and psychic moans' --> corneal calcification --> shortened QT interval on ECG --> hypertension

Answer 110

--> Primary hyperparathyroidism: Most common in non-hospitalized patients. --> Malignancy: Most common in hospitalized patients, including causes like PTHrP from tumors, bone metastases, and myeloma.

Answer 111

--> PTHrP: Produced by tumors such as squamous cell lung cancer. --> Bone metastases: Can lead to hypercalcemia. --> Myeloma: Causes increased osteoclastic bone resorption due to cytokines like IL-1 and tumor necrosis factor.

Answer 112

Measuring parathyroid hormone (PTH) levels.

Answer 113

Drugs: thiazides, calcium-containing antacids Sarcoidosis Vitamin D intoxication Granulomas (e.g., tuberculosis, histoplasmosis) Acromegaly Thyrotoxicosis Milk-alkali syndrome Dehydration Addison's disease Paget's disease of the bone: Hypercalcemia may occur with prolonged immobilization.

Answer 114

Rehydration with normal saline, typically 3-4 liters per day.

Answer 115

--> Bisphosphonates: Take 2-3 days to start working, with maximal effect at 7 days. --> Calcitonin: Provides a quicker effect than bisphosphonates. --> Steroids: Used specifically for hypercalcemia due to sarcoidosis.

Answer 116

Loop diuretics may be used if patients cannot tolerate aggressive fluid rehydration. They should be used with caution as they can worsen electrolyte derangement and volume depletion.

Answer 117

Tetany: Muscle twitching, cramping, and spasm Perioral paraesthesia: Tingling around the mouth Chronic symptoms: Depression, cataracts ECG: Prolonged QT interval

Answer 118

Definition: Carpal spasm induced by occluding the brachial artery with a blood pressure cuff. Method: Inflate the cuff above systolic pressure and maintain it. Appearance: Wrist flexion and fingers drawn together. Prevalence: Seen in around 95% of patients with hypocalcemia and around 1% of normocalcemic people.

Answer 119

Definition: Facial muscle twitching in response to tapping over the parotid gland. Prevalence: Seen in around 70% of patients with hypocalcemia and around 10% of normocalcemic people.

Answer 120

Vitamin D deficiency (e.g., osteomalacia) Chronic kidney disease Hypoparathyroidism (e.g., post thyroid/parathyroid surgery) Pseudohypoparathyroidism (target cells insensitive to PTH) Rhabdomyolysis (initial stages) Magnesium deficiency (due to end-organ PTH resistance) Massive blood transfusion Acute pancreatitis Contamination: Blood samples contaminated with EDTA can cause falsely low calcium levels.

Answer 121

--> Intravenous calcium replacement: Preferred method is intravenous calcium gluconate, 10 ml of 10% solution over 10 minutes. --> Alternative: Intravenous calcium chloride, though more likely to cause local irritation. --> Monitoring: ECG monitoring is recommended during treatment. Further management: Depends on the underlying cause of hypocalcemia.

Answer 122

Hypothermia is an unintentional reduction in core body temperature below normal physiological limits. Mild hypothermia: 32-35°C Moderate or severe hypothermia: < 32°C

Answer 123

Exposure to cold in the environment Inadequate insulation in the operating room Cardiopulmonary bypass Newborn babies

Answer 124

General anaesthesia Substance abuse Hypothyroidism Impaired mental status Homelessness Extremes of age

Answer 125

Mild: Shivering, cold and pale skin, slurred speech, tachypnoea, tachycardia, hypertension Moderate: Respiratory depression, bradycardia, hypotension, confusion/impaired mental state Severe: Severe confusion, impaired mental status, potential cardiac arrest

Answer 126

Temperature (low-reading rectal thermometers or thermistor probes) 12-lead ECG (look for ST-elevation and J waves) FBC and serum electrolytes Blood glucose Arterial blood gas Coagulation factors Chest X-ray

Answer 127

Remove from the cold environment and wet/cold clothing Warm with blankets Secure airway and monitor breathing If needed, use warm IV fluids or forced warm air Be prepared for CPR if severe; avoid IV drugs if possible

Answer 128

Do not put them into a hot bath Do not massage their limbs Do not use heating lamps Do not give them alcohol to drink

Answer 129

bradycardia 'J' wave (Osborne waves) - small hump at the end of the QRS complex first degree heart block long QT interval atrial and ventricular arrhythmias

Answer 130

--> Insulinoma: Increased ratio of proinsulin to insulin --> Self-administration of insulin/sulphonylureas --> Liver failure --> Addison's disease --> Alcohol: Increases insulin secretion due to effects on pancreatic blood flow --> Nesidioblastosis: Beta cell hyperplasia

Answer 131

Hormonal Response: Decreased insulin secretion, increased glucagon, later increased growth hormone and cortisol Sympathoadrenal Response: Increased catecholamine (adrenergic) and acetylcholine (cholinergic) neurotransmission

Answer 132

<3.3 mmol/L: Autonomic symptoms (sweating, shaking, hunger, anxiety, nausea) <2.8 mmol/L: Neuroglycopenic symptoms (weakness, vision changes, confusion, dizziness) Severe/Uncommon Features: Convulsion, coma

Answer 133

Initial Treatment: Oral glucose (10-20g in liquid, gel, or tablet form) Alternatives: Quick-acting carbohydrate (e.g., GlucoGel, Dextrogel) For severe cases: HypoKit containing glucagon for IM or SC injection

Answer 134

If Alert: Quick-acting carbohydrate (glucogel/dextrogel) If Unconscious or Unable to Swallow: Glucagon: Subcutaneous or intramuscular injection Alternatively: Intravenous 20% glucose solution through a large vein

Answer 135

Hypothyroidism affects around 1-2% of women in the UK and is 5-10 times more common in females than males.

Answer 136

--> Hashimoto's Thyroiditis: Most common cause, an autoimmune disease, often associated with IDDM, Addison's disease, or pernicious anemia; may cause transient thyrotoxicosis in acute phase --> Subacute Thyroiditis (de Quervain's): Inflammatory condition --> Riedel Thyroiditis: Fibrous thyroiditis --> Post-Thyroidectomy or Radioiodine Treatment: Removal or destruction of thyroid tissue -->Drug Therapy: Lithium, amiodarone, anti-thyroid drugs (e.g., carbimazole) -->Dietary Iodine Deficiency: Lack of iodine in the diet

Answer 137

Down's Syndrome Turner's Syndrome Coeliac Disease

Answer 138

Weight gain Lethargy Cold intolerance

Answer 139

Dry (anhydrosis), cold, yellowish skin Non-pitting oedema (e.g., hands, face) Dry, coarse scalp hair Loss of lateral aspect of eyebrows

Answer 140

Constipation

Answer 141

Menorrhagia

Answer 142

Decreased deep tendon reflexes Carpal tunnel syndrome

Answer 143

Hoarse voice

Answer 144

-->Initial Dosage: Elderly patients and those with ischemic heart disease: Start with 25 mcg daily, slowly titrate. Other patients: Start with 50-100 mcg daily. --> Monitoring: Check thyroid function tests 8-12 weeks after changing the levothyroxine dose. Aim for a TSH level in the range of 0.5-2.5 mU/L. -->Pregnancy: Increase levothyroxine dose by 25-50 mcg for pregnant women with established hypothyroidism. Monitor TSH carefully during pregnancy, aiming for a low-normal value.

Answer 145

-->Side Effects: Over-treatment can lead to hyperthyroidism, reduced bone mineral density, worsening angina, and atrial fibrillation.

Answer 146

--> Drug Interactions: Iron reduces levothyroxine absorption; take them at least 2 hours apart.

Answer 147

Underweight: < 18.49 kg/m² Normal: 18.5 - 25 kg/m² Overweight: 25 - 30 kg/m² Obese Class 1: 30 - 35 kg/m² Obese Class 2: 35 - 40 kg/m² Obese Class 3: > 40 kg/m²

Answer 148

--> Conservative: Diet and exercise --> Medical - Orlistat: A pancreatic lipase inhibitor Liraglutide: A GLP-1 mimetic --> Surgical: Reserved for specific cases of severe obesity

Answer 149

BMI of ≥ 28 kg/m² with associated risk factors (T2DM, hypertension or hypercholesterolaemia), or BMI of ≥ 30 kg/m² Only be continued if weight loss (e.g. ≥ 5% after 3 months) Usually prescribed for < 1 year

Answer 150

BMI ≥ 35 kg/m² Prediabetic hyperglycaemia (e.g., HbA1c 42 - 47 mmol/mol) Administered as a daily subcutaneous injection

Answer 151

Osteoporosis is a complex, progressive skeletal disease characterized by reduced bone mineral density and defects in bone tissue micro-architecture, leading to an increased risk of fragility fractures.

Answer 152

Postmenopausal osteoporosis (Type I): Linked to decreased estrogen levels. Age-related osteoporosis (Type II): Occurs naturally with aging

Answer 153

Hyperthyroidism Hyperparathyroidism Alcohol abuse Immobilisation

Answer 154

Men generally have greater bone mass at any age and do not experience a menopause equivalent, while post-menopausal women face increased bone tissue degradation due to decreased estrogen levels.

Answer 155

Oral bisphosphonates Lifestyle modification: Exercise and vitamin D supplements Monoclonal antibody treatment (for some patients to prevent further reduction in bone mineral density)

Answer 156

Bone density: Amount of bone present. Bone quality: Trabeculization of bone.

Answer 157

The FRAX tool is used to calculate the 10-year risk of a major osteoporotic fracture and a hip fracture, based on various risk factors.

Answer 158

Age (between 40 and 90 years) Gender Previous fracture Parent with fractured hip Smoking Glucocorticoid use (>3 months at a dose of prednisolone 5mg daily) Rheumatoid arthritis Secondary osteoporosis Alcohol consumption Bone Mineral Density (BMD)

Answer 159

Anyone on long-term oral corticosteroids or with a previous fragility fracture Anyone >= 50 with risk factors All women over 65 All men over 75

Answer 160

Taking glucocorticoids for more than 3 months, especially at doses of prednisolone 5mg daily or higher, is associated with increased bone loss, raising the risk of fractures.

Answer 161

--> Oestrogen deficiency: Increased number of remodelling units. Premature arrest of osteoblasts, leading to perforation of trabeculae. Loss of fracture resistance. --> Glucocorticoids: Initial phase: High-turnover state with increased fracture risk within 3 months. Prolonged use: Reduced bone synthesis by osteoblasts, leading to net bone loss. Common with prednisolone doses of 10mg daily for 3 months or more. --> Ageing: Increased bone turnover at the bone/vascular interface in cortical bone, leading to trabeculization of cortical bone and weak long bone structure.

Answer 162

--> Typical presentation: Osteoporosis often remains asymptomatic during its latent period, with fragility fractures being the first clinical sign. These occur most frequently in older women, with a sharp increase in prevalence from 2% at 50 years to 25% by 80 years. Common pathological fractures: --> Vertebral compression fractures: Acute back pain, worsened by prolonged standing or bending. Thoracic kyphosis (Dowager’s hump) from anterior compression fractures. Only 1 in 3 vertebral fractures are symptomatic. --> Appendicular fractures: Proximal femur (hip): Hip pain, inability to bear weight, shortened and externally rotated leg. Distal radius (Colles): Wrist pain and reduced movement after a fall on an outstretched hand. Complications: --> Post-operative recovery often complicated by co-morbidities (e.g., pneumonia, DVT).

Answer 163

--> Evaluate bone density loss. --> Exclude secondary causes of bone loss. --> Monitor therapy/preventative intervention effectiveness. Bone mineral density measurement: Dual-energy X-ray absorptiometry (DXA): Measures bone mineral density using low radiation. T-score interpretation: -1.0 = Normal. -1.0 to -2.5 = Osteopenia. < -2.5 = Osteoporosis. Secondary cause investigations: Quantitative CT/US of heel. Lab tests: FBC, U&Es, LFTs, TFTs, 25-OH vitamin D, testosterone. Radiographs: Lumbar/thoracic spine for fractures. Additional: Protein electrophoresis, urinary Bence-Jones protein.

Answer 164

--> Osteoporosis: Decreased density of normally mineralized bone matrix, often asymptomatic until fractures occur. --> Osteomalacia: Insufficient bone mineralization; may have variable BMD, causes generalized bone pain, tenderness, and myopathy.

Answer 165

--> Osteoporosis: Decreased bone mass with normal bone structure, increased fracture risk. --> Paget Disease: Excessive osteoclastic bone resorption and compensatory osteoblast formation. New bone is weaker (mosaic pattern), leading to deformities, bone and joint pain, and neurological complications.

Answer 166

--> Osteoporosis: Normal serum calcium, phosphate, alkaline phosphatase (ALP), and parathyroid hormone (PTH). --> Osteomalacia: Decreased serum calcium and phosphate, increased ALP and PTH. --> Paget Disease: Normal serum calcium and phosphate, increased ALP, normal PTH.

Answer 167

Hyperparathyroidism. Mastocytosis. Sickle cell anemia. Myeloma and other neoplastic bone diseases (e.g., primary or metastatic tumors, lymphoma).

Answer 168

--> Falls risk assessment --> Weight-bearing and muscle strengthening exercises --> Ensure daily intake of calcium (800-1200mg) and vitamin D (400-800 IU) --> Calculate 10-year fracture risk (FRAX) --> Lifestyle Modification: Encourage exercise and sufficient vitamin D and calcium intake. --> Pharmacological Therapy: Oral bisphosphonates (Alendronate or Risedronate) for high fracture risk (>1% on FRAX). Denosumab for extensive osteoporosis (subcutaneous injection every 6 months). Hormone Replacement Therapy (HRT) for early postmenopausal women (reserved use due to breast cancer and cardiovascular risks). --> Specific Treatments: Glucocorticoid-Induced Osteoporosis: Start bone-protection at glucocorticoid therapy onset. Osteoporosis in Men: Bisphosphonates first-line, Denosumab alternative for those intolerant. --> Fracture Management: Bed rest, strong analgesia, and physiotherapy for vertebral fractures.

Answer 169

Osteomalacia is caused by a deficiency of vitamin D, leading to softening and weakening of bones.

Answer 170

--> High doses of vitamin D supplements --> Calcium supplements --> Lifestyle changes like increased sun exposure and dietary modifications

Answer 171

Musculoskeletal Symptoms: Bone pain: Diffuse, poorly localized, typically affecting lower back, hips, pelvis, and lower extremities. Muscle weakness: Proximal weakness, especially in lower limbs, causing difficulty climbing stairs or walking. Joint pain: Arthralgia, especially in large joints like hips and shoulders. Fractures: Insufficiency fractures from minimal trauma or spontaneously. Skeletal Deformities: Pseudofractures (Looser's zones): Radiolucent bands indicating unmineralized osteoid. Bowing deformities: Seen in long bones such as femur and tibia. Spinal deformities: Vertebral compression fractures may cause kyphosis or scoliosis. Neurological Manifestations: Paresthesia: Numbness or tingling in extremities due to hypocalcemia. Tetany: Carpopedal spasm, Chvostek’s or Trousseau’s sign due to severe hypocalcemia. Extra-skeletal Manifestations: Dental abnormalities: Dental caries, enamel hypoplasia, and periodontal disease. Nonspecific symptoms: Fatigue, anorexia, and weight loss.

Answer 172

By Size: --> Microadenoma: <1cm --> Macroadenoma: ≥1cm By Hormonal Status: --> Secretory/Functioning: Produces excess hormones --> Non-Secretory/Non-Functioning: Does not produce excess hormones

Answer 173

--> Prolactinomas (most common): Excess prolactin production --> Non-Secreting Adenomas --> Growth Hormone (GH) Secreting Adenomas: Cause acromegaly --> Adrenocorticotropic Hormone (ACTH) Secreting Adenomas: Cause Cushing’s disease

Answer 174

--> Hormonal excess: Cushing's disease (ACTH), acromegaly (GH), amenorrhea and galactorrhea (prolactin) --> Hormonal deficiency: Generalized hypopituitarism --> Dura stretching: Headaches --> Optic chiasm compression: Bitemporal hemianopia

Answer 175

--> Pituitary blood profile (GH, prolactin, ACTH, FSH, LSH, TFTs) --> Formal visual field testing --> MRI brain with contrast

Answer 176

Pituitary hyperplasia Craniopharyngioma Meningioma Brain metastases Lymphoma Hypophysitis Vascular malformation (e.g., aneurysm)

Answer 177

--> Medical Therapy: Prolactinomas: Dopamine agonists (cabergoline, bromocriptine) GH-secreting adenomas: Somatostatin analogues, GH receptor antagonists ACTH-secreting adenomas: Cortisol synthesis inhibitors, neuromodulators --> Surgery: Transsphenoidal surgery (primary treatment) --> Radiotherapy: For residual or recurrent tumors after surgery

Answer 178

SIADH is characterized by hyponatraemia due to the dilutional effects of excessive water retention, with patients typically being euvolemic, meaning they do not show signs of overt volume depletion or overload.

Answer 179

--> Excessive ADH (vasopressin) release leads to water retention, volume expansion, and dilutional hyponatraemia. --> ADH increases water reabsorption in kidney collecting ducts, decreasing urine output. --> In SIADH, ADH release continues despite normal/excess body fluid levels, leading to excessive water retention without signs of fluid overload (e.g., oedema, hypertension). --> Dilution of electrolytes, especially sodium, causes hyponatraemia.

Answer 180

Malignancy: --> Small cell lung cancer Also: pancreas, prostate cancers Neurological: --> Stroke, subarachnoid/subdural haemorrhage --> Meningitis, encephalitis, abscess Infections: --> Tuberculosis --> Pneumonia Drugs: --> Sulfonylureas, SSRIs, tricyclics --> Carbamazepine, vincristine, --> cyclophosphamide Other Causes: Positive end-expiratory pressure (PEEP) Porphyrias MOST IMPORTANT TO REMEMBER: 2S2P mnemonic SSRIs Small cell lung cancer Pneumonia Post-surgery

Answer 181

Headache Fatigue Muscle aches and cramps Confusion

Answer 182

--> Urine osmolality: Inappropriately high (>100 mOsm/kg), as urine should be more diluted with low serum osmolality. --> Urine sodium concentration: Typically high (>40 mmol/L) due to ADH's effect on renal tubules.

Answer 183

--> Slow correction of hyponatraemia: To avoid central pontine myelinolysis. --> Fluid restriction. --> Demeclocycline: Reduces responsiveness of renal tubule cells to ADH. --> ADH receptor antagonists may also be used.

Answer 184

It is an autoimmune disorder where immune cells infiltrate the extraocular muscles and orbital connective tissues, leading to inflammation, oedema, and fibrosis, which can cause proptosis, diplopia, restrictive strabismus, exposure keratopathy, and potentially compressive optic neuropathy.

Answer 185

Mild: Eyelid retraction. Severe: Proptosis, diplopia, restrictive strabismus, exposure keratopathy, and sight-threatening compressive optic neuropathy.

Answer 186

Clinical examination: Signs like lid lag or Von Graefe's sign. Imaging: CT or MRI orbits to assess muscle involvement. Serological tests: For thyroid function.

Answer 187

Medical: Corticosteroids are the first-line treatment during the active phase to reduce inflammation. Surgical: Orbital decompression surgery may be necessary for optic nerve compression or severe proptosis causing corneal breakdown.

Answer 188

--> Exophthalmos (proptosis or bulging eyes) --> Conjunctival oedema --> Optic disc swelling --> Ophthalmoplegia (restricted eye movement)

Answer 189

Sore, dry eyes due to exposure. If severe and untreated, patients are at risk of exposure keratopathy.

Answer 190

Topical lubricants are used to prevent corneal inflammation caused by exposure.

Answer 191

Steroids are used to reduce inflammation, particularly during the active phase of the disease.

Answer 192

Radiotherapy: May be used to reduce inflammation. Surgery: Indicated for severe cases, such as optic nerve compression or significant proptosis.

Answer 193

Multinodular goitre Thyroid adenoma Hashimoto's thyroiditis Cysts (colloid, simple, or hemorrhagic)

Answer 194

Papillary carcinoma (most common malignant cause) Follicular carcinoma Medullary carcinoma Anaplastic carcinoma Lymphoma

Answer 195

Thyroid function tests should be done in all patients. Ultrasonography is the first-line imaging to assess for features suspicious of malignancy.

Answer 196

Weight loss Feeling "manic" or restless Heat intolerance

Answer 197

Palpitations and tachycardia High-output cardiac failure, especially in elderly patients Rarely, reversible cardiomyopathy

Answer 198

Increased sweating Pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli Thyroid acropachy: clubbing

Answer 199

Oligomenorrhea (infrequent menstrual periods)

Answer 200

Anxiety Tremor

Answer 201

Graves' disease is an autoimmune condition where antibodies form against thyroid-stimulating hormone (TSH), leading to overproduction of thyroid hormones. It is the most common cause of hyperthyroidism in developed countries.

Answer 202

--> Type 1 diabetes mellitus --> Addison’s disease --> Pernicious anaemia

Answer 203

Graves' disease involves a type II hypersensitivity reaction, where IgG antibodies bind to TSH receptors on thyroid follicular cells, causing chronic stimulation.

Answer 204

Chronic stimulation of the TSH receptor in Graves' disease results in: Excessive production of thyroid hormones (T3 and T4) Hypertrophy of the thyroid gland Hyperplasia of thyroid follicular cells Signs and symptoms of hyperthyroidism and goitre

Answer 205

Heat intolerance: Increased metabolism raises body temperature. Weight loss: Due to a higher metabolic rate. Increased appetite: Seen in 90% of patients, usually without weight gain. Excessive sweating: Must be differentiated from post-menopausal hot flushes.

Answer 206

Palpitations: Including atrial fibrillation or other supraventricular tachycardias, especially in older patients. Tachycardia Atrial fibrillation Hypertension Heart failure: Thyrotoxic cardiomyopathy, particularly in the elderly.

Answer 207

Anxiety: Feeling of nervousness and trembling. Tremor: Typically fine.

Answer 208

Palpable thyroid: Smooth, diffusely and uniformly enlarged goitre. Oligomenorrhoea

Answer 209

Eye disease (30%): Includes upper eyelid retraction, exophthalmos, ophthalmoplegia, eye pain, tearing, diplopia, photophobia, and blurred vision. Pretibial myxoedema (3%): Waxy, discoloured induration on the anterior lower legs. Thyroid acropachy (1%): Clubbing of fingers and toes, with soft tissue swelling due to sub-periosteal bone formation.

Answer 210

Step 1: Test for thyroid dysfunction. Tests include: TSH: Low in hyperthyroidism. Free thyroxine (fT4): High in hyperthyroidism. Free triiodothyronine (fT3): High in hyperthyroidism. Consider repeating tests if symptoms worsen or new symptoms develop (at least 6 weeks after the previous test).

Answer 211

Step 2: If hyperthyroidism is confirmed, test for Graves’ disease. Specific tests for Graves' disease: TSH receptor antibodies (TRAbs): Present in Graves’ disease with a sensitivity >97% and specificity >98%. Technetium scan: Considered if TRAbs are negative.

Answer 212

--> Imaging is considered if a discrete thyroid nodule is palpated. Options include: Ultrasound scan: Assesses size, vascularity, and nodules (enlarged, hypervascular thyroid with nodules in ~15% of Graves’ patients). Radioactive iodine scan: Diffuse and high uptake: Suggests Graves’. Uneven uptake: Indicates a nodule. Low uptake: Suggests thyroiditis.

Answer 213

Examine visual fields, acuity, and eye movements. MRI or CT scans: Can confirm diagnosis, especially in subclinical cases.

Answer 214

Perform an ECG to assess for potential cardiac complications.

Answer 215

--> ß-blockers: Use: Control symptoms (e.g., palpitations). Example: Propranolol. --> Antithyroid Drugs: First-line: Carbimazole or Propylthiouracil. Duration: 12-18 months; used if remission is likely or other treatments are unsuitable. Radioactive Iodine: --> First-line: Preferred for most patients. Avoid: Pregnancy, active eye disease, or malignancy concerns. Surgery: Indications: Compression, malignancy concerns, or if other treatments fail. Risks: Potential nerve damage; may require replacement therapy. Children/Young People: Antithyroid drugs for at least 2 years; refer to paediatric endocrinology. Care Setting: Antithyroid drugs and ß-blockers can start in primary care; comprehensive management in secondary care.

Answer 216

Agranulocytosis